PB2159: CHARACTERIZATION OF THE IMMUNE RESPONSE DEVELOPED IN PATIENTS WITH MULTIPLE MYELOMA AFTER RECEIVING TWO DOSES OF THE VACCINE AGAINST SARS-COV-2
Authors: Laura Perez, Miriam Solera, Magdalena Corona, Montserrat Torres, Guiomar Casado, Clara Sánchez-Menéndez, Alejandro Zurdo, Javier Garcia, Maria Aranzazu Murciano, Maria Teresa Pérez, Valentin Garcia Gutierrez, Maria Teresa Coiras, Sara Rodríguez Mora
Journal: HemaSphere (2023)

Topic: 14. Myeloma and other monoclonal gammopathies - Clinical Background: Individuals with oncohematological malignancies may present an altered response to vaccines against COVID-19 and are especially susceptible to infection with SARS-CoV-2. However, they have been generally excluded from clinical trials performed for the approval of these vaccines. Individuals with multiple myeloma (MM) are not an exception and they may develop a more acute form of SARS-CoV-2 infection due to their disease and/or the treatments that they receive. Aims: To analyze the humoral and cellular immune responses of individuals with MM before and 3 weeks after receiving the full vaccination schedule against SARS-CoV-2. Methods: Both humoral and cellular immune responses against SARS-CoV-2 were analyzed in a population of 19 patients with MM and 10 healthy donors before and 3 weeks after receiving the complete vaccination schedule against COVID-19. Studies to characterize the humoral response were performed by titrating IgGs against SARS-Co-2 with an ELISA assay (Euroimmun) and neutralization assays were performed using a pseudotyped SARS-CoV-2 virus. Total B lymphocytes in peripheral blood cells (PBMCs) was quantified by flow cytometry. Antibody-dependent cellular cytotoxicity (ADCC) was evaluated using rituximab-coated Raji cells cocultured with PBMCs of the participants and the induction of apoptosis was quantified in the target cells by staining with Annexin V. Direct cellular cytotoxicity (DCC) of the PBMCs against Vero E6 cells infected with pseudotyped SARS-CoV-2 was also analyzed by quantifying Caspase-3 activation in the monolayer. Results: 1) Individuals with MM and healthy donors showed similar early humoral response against COVID-19, which was increased 5-fold (p <0.0001) 3 weeks after receiving the full vaccination schedule in both groups. 2) We did not observe significant differences in neutralizing antibody titers against SARS-Cov-2, between individuals with MM and healthy donors. 3) The study of total levels of B lymphocytes showed acute lymphopenia in individuals with MM (5% CD19+), in comparison with healthy donors (11% CD19+). 4) ADCC analysis showed that the levels of apoptosis in the target cells were similar in both study populations, although MM patients showed a higher response than healthy controls. 5) DCC analysis showed higher activity in PBMCs from MM patients in comparison with healthy donors before and three weeks after full vaccination schedule (p<0.0001). Summary/Conclusion: Unlike other patients with OHM, individuals with MM showed an increased humoral and cellular response that was comparable or even higher than healthy donors. This enhanced immunity could be related to the cancerous process and/or to treatment with immunomodulatory drugs such as lenalidomide that may increase the cytotoxic response. Keywords: COVID-19, Vaccination, Myeloid leukemia